Contribution of two different mechanisms to erythromycin resistance in Escherichia coli

Escherichia coli BM2570 was resistant to high levels of erythromycin by two different mechanisms. The two genes conferring resistance to erythromycin in BM2570 were carried by a 150-kilobase self-transferable plasmid, pIP1527, and were cloned separately in E. coli. A single polypeptide with an Mr of 27,000 was encoded by the gene erxA and conferred high-level resistance to macrolide, lincosamide, and streptogramin B-type antibiotics by a mechanism other than drug inactivation. This resistance phenotype, not previously reported for a clinical isolate of enterobacteria, was probably due to modification of the ribosomes. The gene ereB encoded an enzyme with an Mr of 51,000 which inactivated erythromycin and oleandomycin. The two different mechanisms specified by erxA and ereB contributed in more than an additive fashion to the high level of resistance to erythromycin conferred by plasmid pIP1527 to E. coli BM2570.